Consumers continually seek to improve the appearance of their skin and in particular to reduce appearance of skin affected by unwanted deposition and/or accumulation of fat, including cellulite. There is active interest in the cosmetics industry to develop products that may be applied topically to the skin to provide anti-cellulite benefits, as well as other anti-lipid benefits. Cosmetic products that enhance the appearance of skin are increasingly in demand as consumers increasingly seek to mitigate and delay signs of excess accumulation and/or production of subcutaneous fat.
Peroxisome proliferator-activated receptor-gamma (PPAR-γ) is a member of the nuclear receptor family of transcription factors involved in the regulation of lipid biosynthesis. PPAR-y heterodimerizes with retinoid X receptor (RXR), leading to transactivation of genes that encode proteins involved in adipogenesis. PPAR-γ agonists (e.g. rosiglitazone) have been shown to increase fat synthesis and storage in adipocytes; whereas lipid accumulation and adipocyte differentiation are impaired when PPAR-γ levels are reduced.
Stearoyl-CoA desaturase-1 (SCD1) is a key lipogenic enzyme that catalyzes the synthesis of monounsaturated fatty acids. Its preferred desaturation substrates are palmitoyl-CoA and stearoyl-CoA, which are converted to palmitoleoyl-CoA and oleoyl-CoA, respectively. Oleic acid constitutes nearly half of the total fatty acids in the adipose tissue (de Vries, Am J. Clin Nutrition. 1991; 53:469-73). The absence of SCD1 leads to reduced triglycerides synthesis, decreased lipid storage, and decreased lipid export. Further, SCD1-deficient mice have shown that loss of SCD1 increases the expression of genes involved in fatty acid oxidation and reduces the expression of lipogenic genes. As a result of changes in gene expression, SCD1-deficient mice have reduced body fat and increased energy expenditure and oxygen consumption (Ntambi et al. PNAS 2002; 99:1 1482-11486).
Tenascin X is a member of the Tenascin family of proteins, a family of large oligomeric glycoproteins found in the extracellular matrix. Tenascins are responsible for modulating cell-matrix interactions and influencing cell functions. Tenascin-X is expressed in connective tissues, such as skin, joints, and muscles, and plays a critical role in remodeling and maintaining the integrity of skin. Deficiency causes one of the types of Ehlers-Danlos syndrome, a heritable connective tissue disorder characterized by connective tissue defects, such as reduced collagen deposition, different mechanical properties of dense tissues, and fragmentation of elastic fibers in the skin. In vitro studies have demonstrated that tenascin-X deficient fibroblasts fail to deposit collagen type I in the matrix. Further, culture grafting experiments have demonstrated that the expression of tenascin-X is required for the organization of fibrillin I and elastin into a fibrillar network (Zweers et al, 2005, Cell Tissue Res, 319:279). Moreover, tenascin-X deficient mice have been shown to increase lipid accumulation in subcutaneous adipose tissue and reduce the density of collagen fibrils, which is similar to the characteristics of cellulite-affected skin (Ken-ichi Matsumoto et al. 2004, Genes to Cells, 9, 737-748).
Active ingredients derived from plants and plant seeds have commonly been employed for a myriad of medicinal, therapeutic and cosmetic purposes. Such actives may be obtained from the entire plant or various parts of a plant, such as seeds, needles, leaves, roots, bark, cones, stems, rhizomes, callus cells, protoplasts, organs, organ systems, and meristems. Active ingredients can be incorporated in compositions in a variety of forms. Such forms include a pure or semi-pure component, a solid or liquid extract or derivative, or a solid natural plant material. Plant material also may be incorporated in a variety of sub-forms such as whole, minced, ground or crushed. A common problem when using an active ingredient derived from a plant material and/or plant seed, however, is the relatively low level at which they naturally occur. Such low levels frequently require relatively large amounts of the natural plant material be processed in order to obtain desired or useful quantities of actives, and specific extraction procedures may be required.
Eclipta prostrata Linn., also known as Eclipta alba (L) Hassk, of the Family Astraceae, is a common plant found growing in moist soils throughout India and can reach a height of about 6,000 ft. Eclipta prostrata is used in traditional Indian medicines, e.g., as to treat cirrhosis of the liver and infective hepatitis (Dixit, S. P. et al. Journal of Scientific Research in Plants and Medicines 1981, 2, 96-100). In addition, the plant is used to treat hyperglycemia and hyperlipidemia by inhibiting, it is believed, gluconeogenesis and possibly also modulating lipid metabolism and excretion in the liver. A topical cosmetic composition having an active ingredient derived from a plant material, or extract thereof, would be desired in improving the appearance of skin in the treatment, control, management, amelioration, prevention, inhibition, delay, and/or reduction of excess accumulation and/or production of subcutaneous fat, including cellulite.
Cellulite is the lumpy uneven type of subcutaneous fat that tends to accumulate on the buttocks, thighs, and limbs of many women. It is considered unsightly because it gives the tissues underlying the skin an “orange peel” or “cottage cheese” look. Compressing the skin, as when sitting or crossing the legs, produces a “mattress appearance” with bulging and pitting of the fatty layer. Nodules of fat may be felt trapped within hardened connective tissue. The histology of cellulite-affected skin indicates that cellulite results from a combination of enlarged fat tissue and weak dermal structure and connective tissue septa. Excess fat accumulation increases the volume of adipocytes, which bulge into a weakened dermis to create the characteristic irregularities in the appearance of the epidermal surface. A number of factors can cause cellulite including, e.g., hereditary, intestinal, circulatory, lymphatic, hormonal, and lifestyle factors. Dieting to decrease fat intake, exercise to increase fat metabolism and prevent the build up of cellulite, and massage and hydrotherapy to stimulate lymphatic drainage can help reduce the appearance of cellulite. Nonetheless, these means for combating cellulite or subcutaneous fat are limited, and the need remains for additional approaches.
Therefore, safe, effective, natural, and new ingredients to treat, ameliorate, prevent: inhibit, delay, and/or reduce the signs of excess accumulation and/or production of subcutaneous fat, and/or improve dermal architecture by strengthening connective tissue, would be advantageous for topical compositions useful as skin products. Novel methods and compositions, as well as their mode of action, are provided herein for treating conditions related to excess accumulation and/or production of subcutaneous fat, including cellulite, as well as skin formulations comprising same, and other personal care products for the skin.
The foregoing discussion is presented solely to provide a better understanding of nature of the problems confronting the art and should not be construed in any way as an admission as to prior art nor should the citation of any reference herein be construed as an admission that such reference constitutes “prior art” to the instant application.